This application requests funding to support the purchase of a state-of-the-art PET-SPECT-CT imaging system. This triple modality imager will actively support NIH-funded research addressing questions of fundamental importance in fields of experimental pharmacology, tumor biology, molecular imaging, and cognitive neuroscience. Massachusetts General Hospital has long a history of developing and conducting imaging research involving different isotope-based techniques, functional MRI, and optical imaging. Recently, the need for high-resolution imaging in small animal models has escalated, especially, the need for combined imaging modalities. Isotope-based imaging with PET and SPECT techniques enables functional imaging of the distribution of radio labeled ligands to measure physiological parameters such as blood flow, metabolism, receptor and/or enzyme function;however, these techniques do not necessarily delineate anatomical borders of tissues or organs, which severely limits interpretation of the data. Anatomical landmarks are extremely important, especially in whole-body imaging of the mouse. Anatomical imaging modalities like CT can provide these landmarks and, in addition, can provide accurate maps for attenuation correction of PET and SPECT data. The combined use of PET and SPECT can be extremely advantageous, for instance, for developing probes for cancer diagnosis and/or therapy. By using PET and SPECT imaging together, one probe can be radio labeled with two isotopes: one for PET and another for SPECT. The isotopes used for SPECT imaging generally have longer half-lives than PET isotopes, enabling long-term follow up studies not possible with PET imaging alone. The combined use of PET and SPECT imaging also enables imaging of metabolism (via PET) and blood flow (via SPECT) in the same imaging session. Currently we do not have instrumentation to allow us to acquire this information simultaneously. Our existing Concord micro PET system, P4, is a primate-size system;its resolution of 2 mm is not high enough to support imaging studies in mouse brain. We have used this PET system extensively for studies in the primate brain. We have also used it for imaging studies of xeno transplanted tumors in mouse models, but these studies are hindered by the inability to precisely localize tumor boundaries. A combined system for simultaneous acquisition of PET data with SPECT and CT data would allow us to realize the potential of such studies. Given the exceptional biomedical imaging research community at the MGH, the broad multimodality imaging resources of the Martinos Center, and the existing technical expertise and infrastructure in place, the proposed triple modality PET-CT-SPECT imager would immediately increase the efficiency, accessibility, and innovation of many existing research programs, and contribute to the MGH's strategy for an integrated biomedical imaging research environment. The proposed system manufactured by Siemens is the only triple modality system presently available.